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人類誘導式全功能性幹細胞(iPSC)於腦部損傷之細胞移植治療 Delayed epidural transplantation of human induced pluripotent stem cell-derived neural progenitors enhances functional recovery after stroke

Scientific Reports 7, Article number: 1943 (2017), doi:10.1038/s41598-017-02137-w

http://www.nature.com/articles/s41598-017-02137-w

Induced pluripotent stem cell-derived neural progenitor cells (iPSC-NPCs) are a promising source of tailor-made cell therapy for neurological diseases. However, tumorigenicity and immunogenicity are major obstacles to translational use. To decrease intracerebral complications, we implanted the human iPSC-NPCs epidurally over the peri-infarct cortex at 7 days following permanent middle cerebral artery occlusion in adult rats. The cell-treated rats showed significant improvement in their paretic forelimb usage and grip strength from 10 days post-transplantation (dpt) onwards and ameliorated infarct/atrophy volumes, inflammatory infiltration and astrogliosis at 21 dpt compared to controls. Few human iPSC-NPCs migrated into rat peri-infarct cortices but poorly survived. To elucidate paracrine mechanism of epidural iPSC-NPCs graft, we co-cultured human iPSC-NPCs trans-membranously with rat cortical cells subjected to oxygen-glucose deprivation. Compared to negative and positive controls of other human stem cells, human iPSC-NPCs superiorly enhanced rat neural survival and outgrowth as well as mitigated astrogliosis. Using comparative whole-genome microarrays and cytokine neutralization, we identified a neurorestorative secretome from iPSC-NPCs and neutralization of certain enriched cytokines abolished the neuroprotective effects in the iPSC-NPC co-cultures. This proof-of-concept study demonstrates a relatively safe yet effective epidural delivery route of human iPSC-NPCs may promote functional recovery after stroke predominantly through distinct paracrine effects.

 


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115台北市南港區研究院路二段128號
Tel: 02-27899515
Fax: 02-27858059
icob@gate.sinica.edu.tw
Copyright © ICOB 2013. All rights reserved. 最佳瀏覽網頁方式請用最新版IE11或其他瀏覽器 /瀏覽人數:1017284--
 瀏覽人數:1017284